Pro-opiomelanocortin is present in high levels in the pituitary and is processed into 3 major peptide families: adrenocorticotrophin (ACTH); alpha-, beta- and gamma-melanocyte- stimulating hormones (MSH); and beta-endorphin [ (PUBMED:2266117) ]. ACTH regulates the synthesis and release of glucocorticoids and, to some extent, aldosterone in the adrenal cortex. It is synthesised and released in response to corticotrophin-releasing factor at times of stress (i.e. heat, cold, infection, etc.), its release leading to increased metabolism. The action of MSH in man is poorly understood, but it may be involved in temperature regulation [ (PUBMED:2266117) ]. Full activity of ACTH resides in the first 20 N-terminal amino acids, the first 13 of which are identical to alpha-MSH [ (PUBMED:2266117) (PUBMED:2839146) ].
The function of this region is not known, though it is found near the centre of these proteins.
Family alignment:
There are 3062 ACTH_domain domains in 1577 proteins in SMART's nrdb database.
Click on the following links for more information.
Evolution (species in which this domain is found)
Taxonomic distribution of proteins containing ACTH_domain domain.
This tree includes only several representative species. The complete taxonomic breakdown of all proteins with ACTH_domain domain is also avaliable.
Click on the protein counts, or double click on taxonomic names to display all proteins containing ACTH_domain domain in the selected taxonomic class.
Literature (relevant references for this domain)
Primary literature is listed below; Automatically-derived, secondary literature is also avaliable.
Post-translational modification of bovine pro-opiomelanocortin. Tyrosinesulfation and pyroglutamate formation, a mass spectrometric study.
J Biol Chem. 1990; 265: 22130-6
Display abstract
The amino-terminal fragment of beta-lipotropin (i.e. beta-lipotropin (1-40)) and joining peptide portions of pro-opiomelanocortin have been purified from extractsof bovine posterior pituitaries. Peptides were purified using a combination ofreversed-phase and ion-exchange batch extraction procedures followed byreversed-phase high performance liquid chromatography. beta-Lipotropin (1-40) wasfound to consist of four major components while joining peptide was found toconsist of two major components. Fast atom bombardment-mass spectrometricanalysis of the tryptic fragments of both peptides revealed that the observedheterogeneity could be explained in terms of post-translational modifications.beta-Lipotropin (1-40) was found to be sulfated at tyrosine residue 28 to anextent of about 50%. The tyrosine residue in beta-lipotropin (1-40) is situatedwithin an amino acid sequence with a preponderance of glutamate residues.Sulfation of this amino acid residue is entirely compatible with the knownprimary structure requirements of the sulfotransferase enzyme located in thetrans-Golgi fraction. Both beta-lipotropin (1-40) and joining peptide were found to have pyroglutamate at their amino termini to an extent of about 50%. The cDNA sequence for bovine pro-opiomelanocortin predicts the presence of glutamic acidat position 1 of both peptides. Pyroglutamate is normally formed through thecyclization of glutamine. This reaction is thought to be catalyzed by apyroglutamate forming enzyme located within the secretory granule fraction. Undercertain circumstances peptides with glutamate at their amino termini may act assubstrates for this enzyme.
Alpha-amidated peptides derived from pro-opiomelanocortin in normal humanpituitary.
Biochem J. 1988; 250: 781-8
Display abstract
Normal human pituitaries were extracted in boiling water and acetic acid, and thealpha-amidated peptide products of pro-opiomelanocortin (POMC),alpha-melanocyte-stimulating hormone (alpha MSH), gamma-melanocyte-stimulatinghormone (gamma 1MSH), and amidated hinge peptide (HP-N), as well as theirglycine-extended precursors, were characterized by sequence-specificradioimmunoassays, gel-chromatography, h.p.l.c. and amino acid sequencing. alpha MSH and gamma 1MSH constituted 0.27-1.32% and 0.10-5.10%, respectively, of thePOMC-derived products [calculated as the sum of adrenocorticotropic hormone(ACTH)-(1-39), ACTH-(1-14) and alpha MSH immunoreactivity]. alpha MSH andACTH-(1-14) were only present in non- or mono-acetylated forms. Only large forms of gamma 1MSH and gamma 2MSH were present in partly glycosylated states. Thehinge peptides were amidated to an extent two to three orders of magnitudegreater than alpha MSH and gamma 1MSH. Most (99%) of the HP-N was of lowmolecular mass and consisted mainly of HP-N-30. The remaining part washigh-molecular-mass HP-N, probably HP-N-108, although the presence of HP-N-44could not be completely excluded. These results show that all the possibleamidated POMC-related peptides are present in normal human pituitary. It alsoshows that cleavage in vivo at all dibasic amino acids but one, takes place atthe N-terminal POMC region; the exception is at the POMC-(49-50) N-terminal ofthe gamma MSH sequence. The pattern of peptides produced suggests that thegeneration of amidated peptides is mainly regulated at the endopeptidase level.
Links (links to other resources describing this domain)
